Study on the Effect of 4D-CT Special Reconstruction Images for Evaluation of the Cardiac Structure Dose in Radiotherapy for Breast Cancer - Frontiers
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ORIGINAL RESEARCH
published: 31 March 2020
doi: 10.3389/fonc.2020.00433
Study on the Effect of 4D-CT Special
Reconstruction Images for
Evaluation of the Cardiac Structure
Dose in Radiotherapy for Breast
Cancer
Ming Su 1 , Guanzhong Gong 2 , Xiaoping Qiu 1 , Ying Tong 2 , Qian Li 2 and Yong Yin 2*
1
School of Nuclear Science and Technology, University of South China, Hengyang, China, 2 Shandong Cancer Hospital and
Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
Objective: To study the dosimetric effect on special reconstruction images obtained
Edited by: from an electrocardiograph-gated four-dimensional computed tomography (ECG 4D-CT)
Gene A. Cardarelli,
Brown University, United States
series and compare it with the accumulation dose assessment of ECG 4D-CT.
Reviewed by: Methods: Fifteen patients underwent ECG 4D-CT scans to obtain a 4D-CT series.
Sunyoung Jang,
The 20 phase images of 0–95% were reconstructed at intervals of 5% of the cardiac
Princeton Radiation Oncology Center,
United States cycle by the 4D-CT series. The 4D-CT series was specially reconstructed, and the
Tomas Kron, maximum intensity projection (MIP), minimum intensity projection (MinIP), average
Peter MacCallum Cancer
Centre, Australia
intensity projection (AIP), and sum intensity projection (SIP) were obtained. The left
*Correspondence:
ventricular muscle (LV) and the anterior descending branch of the left coronary artery
Yong Yin (LAD) were delineated on all series. The intensity-modulated radiation therapy (IMRT)
yinyongsd@126.com
plan for left breast cancer was designed on the basis of the 0% phase, and the
Specialty section:
accumulative dose (Dose−acc ) of 20 phases was obtained by deformation registration.
This article was submitted to The dose-volume indexes of the LV and LAD were compared based on different
Radiation Oncology, CT series.
a section of the journal
Frontiers in Oncology Results: The dose-volume indices of V5 , V30 , V40 , Dmax , and Dmean of the LV on MIP
Received: 24 September 2019 images were 3.8, 2.0, 0.9, 3.8, and 1.7%, respectively (relative to the Dose−acc ). There
Accepted: 11 March 2020
was no significant difference in V5 or Dmax between the MIP and Dose−acc (P > 0.05).
Published: 31 March 2020
The change rates of Dmax on the MinIP, SIP, and AIP images were 2.5, 3.1, and 1.5%,
Citation:
Su M, Gong G, Qiu X, Tong Y, Li Q respectively (relative to the Dose−acc ) (P < 0.05).
and Yin Y (2020) Study on the Effect
of 4D-CT Special Reconstruction
Conclusion: In the dose-volume evaluation of the LV, V30 , V40 , and Dmean obtained
Images for Evaluation of the Cardiac by MIP were essentially the same as those obtained by the Dose−acc and can be used
Structure Dose in Radiotherapy for
instead of the 4D-CT series to evaluate dose-volume indexes.
Breast Cancer. Front. Oncol. 10:433.
doi: 10.3389/fonc.2020.00433 Keywords: 4D-CT, dose accumulation, special reconstruction, breast cancer, radiotherapy, cardiac structure
Frontiers in Oncology | www.frontiersin.org 1 March 2020 | Volume 10 | Article 433
Su et al. Evaluation the Cardiac Dose for BC
INTRODUCTION ECG 4D-CT Scanning and Reconstruction
Image Acquisition
Breast cancer accounts for 24.2% of new cancer cases Under helical mode, all patients underwent enhanced ECG 4D-
and 15.0% of cancer-related deaths in females. Globally, CT scans at the end of deep inspiratory breath holding (DIBH)
the incidence and mortality of breast cancer rank first with a Siemens dual source CT scanner (Siemens, SOMATOM
in 154 and 104 countries, respectively (1). Radiation Defintion Flash, Germany). At the end of the scan, 20 phases
therapy (RT) is considered a curative-intent treatment for of 0–95% were reconstructed at an interval of 5% of the heart
patients with breast cancer but can cause late locoregional cycle. The CT image matrix size was 512 × 512, the thickness was
complications such as cardiac toxicity, especially for left 0.75 mm, and the interval was 0.5 mm. The ECG 4D-CT images
breast cancer. were transferred to MIM Maestro (Version 6.6.9, MIM, USA)
Radiation-induced heart damage in breast cancer has received for maximum intensity projection (MIP), minimum intensity
much attention. In a recent analysis, Bedi et al. (2) aimed projection (MinIP), average intensity projection (AIP), and sum
to study the differences between treatment plans based on intensity projection (SIP) image reconstruction.
conventional and time-resolved four-dimensional CT. The
results showed that heart movement had a greater impact on
breast cancer radiotherapy than respiratory movement. The
Radiotherapy Design
The 4D-CT images were imported into the Eclipse 13.6 planning
radiation treatment plan based on three-dimensional CT scan
system (Varian Medical System, USA), and the IMRT plan was
well-reflected the dose distribution in the four-dimensional
designed for chest wall, supraclavicular lymph node drainage area
CT derived data set. Using a three-dimensional computerized
and armpit area of each patients with stage of T3–T4, based on
tomography (3D-CT) plan, Budrukkar et al. (3) prospectively
the 0% phase image of each patient. All patients were treated
investigated whether the 3D-CT plan was excellent in terms of
with a 7-field IMRT plan, 2 Gy/Fx, for a total of 50 Gy/25Fx. The
long-term outcomes. However, static 3D-CT does not consider
typical gantry angle configurations were 0◦ , 30◦ , 110◦ , 125◦ , 150◦ ,
the effects of breathing and heartbeat movements on the
310◦ , and 330◦ .
location and shape of the heart, and heartbeat movement is
the main factor affecting the inaccurate dose evaluation of the
heart and its substructure in left breast cancer radiotherapy Delineating the Structure of the Heart
(4, 5). Electrocardiograph-gated four-dimensional computed The 4D-CT series was transmitted to MIM software for
tomography (ECG 4D-CT) provides better image quality and 20 phases and special reconstruction image delineation and
can reduce artifacts caused by the heartbeat motion. Moreover, fusion. The left coronary artery (LAD) and left ventricular
contrast enhancement in ECG 4D-CT is helpful for identifying muscle (LV) were contoured in all 20 phases. The range of
the extent of tissues, which can reduce errors in organ the LV was from the parietal plane of the left ventricle to
delineation (6). ECG 4D-CT is therefore considered to be the apex of the heart, excluding the interventricular septum,
a reliable and effective tool for assessing tumor and organ and the range of the LAD was from the bifurcation of
motion (7).
The prediction of radiation-induced cardiac injury is assessed
by mainly dose-volume indices. ECG 4D-CT provides a basis
for the accurate assessment of cardiac acceptance. However,
the number of ECG 4D-CT images is large, so special
reconstruction can be carried out to reduce the number of
images. Whether special reconstruction images can accurately
assess cardiac volume requires further exploration. In this
study, we explored the accuracy of ECG 4D-CT special
reconstruction images of left breast cancer in assessing cardiac
acceptance. In addition, we compared the cumulative dose
of ECG 4D-CT with that of special reconstruction images in
dose assessment.
MATERIALS AND METHODS
Materials
Fifteen female patients (aged 32–65 years, with a
median age of 49 years) admitted to Shandong Cancer
Hospital between June 14, 2016 and November 15,
2017, were selected as subjects. All patients had no
contraindications to radiotherapy, and all patients
were treated with intensity-modulated radiation FIGURE 1 | Reconstruction sketch. (A) MIP; (B) MinIP; (C) AIP; (D) SIP.
therapy (IMRT).
Frontiers in Oncology | www.frontiersin.org 2 March 2020 | Volume 10 | Article 433Su et al. Evaluation the Cardiac Dose for BC
the left main coronary artery to the apex of the heart RESULTS
(see Figure 1 for details). When delineating window width
(WW)/window level (WL) was 400/40 HU, and WW/WL was Volume Changes in the LV and LAD
slightly adjusted when delineating on special reconstructed ① The volume of the LV showed a decreasing trend on 4D-CT,
images. All the cardiac region of interest (ROI) delineations MinIP, AIP, MIP, and SIP images: (54.55 ± 12.68) cm3 , (53.36 ±
were completed by 3 radiation oncologists reviewing and 12.08) cm3 , (52.05 ± 13.31) cm3 , (50.92 ± 11.10) cm3 , and (42.37
browsing the series of each patient and then jointly developing a ± 9.72) cm3 , respectively. There was a significant difference
delineation standard. between the SIP images and the 4D-CT series (P < 0.05).
② The volume of the LAD showed a decreasing trend on MIP,
AIP, SIP, MinIP, and 4D-CT images: (3.40 ± 0.94) cm3 , (2.24 ±
0.81) cm3 , (1.97 ± 0.86) cm3 , (1.67 ± 0.47) cm3 , and (1.45 ± 0.24)
Deformation Registration cm3 , respectively (P < 0.05). The details are shown in Table 1.
The radiotherapy plan was introduced into MIM software, and
the dose of the 0% phase was mapped to the remaining 19 phases
of the 4D-CT series. The dose of the remaining 19 phases was Dosimetric Changes in the LV
deformed to that of the 0% phase, and the cumulative dose of the In the dosimetric comparison of the LV, the results showed
4D-CT series was obtained, which was named the accumulative that regardless of the kind of special reconstruction method,
dose (Dose-acc). The dose deformation of the 0% phase was half of the dose-volume indexes were not statistically significant
registered into MIP, MinIP, SIP and AIP images. The flow chart is compared with the Dose−acc (P > 0.05). In the MIP images,
shown in Figure 2. the change rates of V10 , V20 , V30 , V40 , Dmin , and Dmean were
6.8, 5.1, 2.0, 0.9, 10.5, and 1.7%, respectively, and the smallest
change rate was that of V40 (0.9%). In the AIP images, the
Data Statistics change rates of V20 , V30 , and Dmean were 17.6, 13.5, and
The dose-volume indexes of the LV and LAD, including 6.2%, respectively, and the smallest change rate was that of
V5 , V10 , V20 , V30 , V40 , Dmin , Dmax , and Dmean , were Dmean (6.2%). However, in MinIP and SIP images, the change
calculated on the MIP, MinIP, SIP, and AIP images and rates were larger than those in the MIP and AIP images (2.5–
4D-CT series, and statistical analyses on the volume of the 19.9% on MinIP images and 3.1–14.0% on SIP images), and
LV and LAD were performed on all series. Analyses were only V10 and V20 were not statistically significant compared
carried out using SPSS 17.0 software, and P < 0.05 was with the Dose−acc (P > 0.05). The details are shown in
considered significant. Table 2.
FIGURE 2 | Dosimetric comparison flow chart.
Frontiers in Oncology | www.frontiersin.org 3 March 2020 | Volume 10 | Article 433Su et al. Evaluation the Cardiac Dose for BC
TABLE 1 | Volume changes in the LV and LAD (x ± s) cm3 .
Organ 4D-CT MinIP AIP MIP SIP P1 P2 P3 P4
LV 54.55 ± 12.68 53.36 ± 12.08 52.05 ± 13.31 50.92 ± 11.10 42.37 ± 9.72 0.217 0.157 0.601 0.004
LAD 1.45 ± 0.24 1.67 ± 0.47 2.24 ± 0.81 3.40 ± 0.94 1.97 ± 0.86 0.001 0.001 0.047 0.011
P1 –P4 represent MIP, AIP, MinIP, and SIP images, respectively, values were derived from the Wilcoxon non-parametric test.
TABLE 2 | Image changes in the dose-volume indexes of the LV (x ± s)%.
LV V5 V10 V20 V30 V40 Dmax Dmin Dmean
MIP 57.26 ± 22.87 38.47 ± 24.36 27.07 ± 19.14 22.69 ± 18.17 13.51 ± 11.86 48.44 ± 4.14 1.72 ± 2.2 14.55 ± 7.06
AIP 59.33 ± 22.62 39.22 ± 24.15 27.99 ± 18.65 23.32 ± 17.79 14.76 ± 10.93 47.52 ± 5.09 1.68 ± 2.02 14.88 ± 6.75
MinIP 59.80 ± 25.80 41.66 ± 23.21 30.27 ± 18.34 24.93 ± 16.81 17.11 ± 12.82 48.36 ± 4.04 1.75 ± 1.85 14.40 ± 7.16
SIP 62.45 ± 22.29 41.67 ± 24.39 31.59 ± 20.60 25.65 ± 17.86 16.58 ± 12.41 49.11 ± 3.92 1.69 ± 2.04 15.12 ± 5.83
Dose−acc 51.10 ± 24.88 31.16 ± 18.45 22.55 ± 16.50 18.18 ± 16.47 13.65 ± 15.56 46.66 ± 5.64 1.55 ± 1.94 12.87 ± 7.70
P1 0.003 0.191 0.211 0.156 0.363 0.011 0.116 0.053
P2 0.022 0.041 0.191 0.078 0.024 0.020 0.036 0.125
P3 0.005 0.053 0.112 0.031 0.035 0.009 0.002 0.394
P4 0.001 0.088 0.061 0.036 0.047 0.011 0.044 0.027
P1 –P4 represent the Dose−acc and MIP, AIP, MinIP, and SIP images; values were derived from the Wilcoxon non-parametric test.
TABLE 3 | Dose-volume changes in the left anterior descending coronary artery (x ± s) %.
LAD V5 V10 V20 V30 V40 Dmax Dmin Dmean
MIP 79.15 ± 18.45 65.88 ± 17.13 57.48 ± 16.32 48.01 ± 17.05 39.13 ± 12.52 48.04 ± 6.01 2.90 ± 2.31 25.39 ± 9.07
AIP 80.60 ± 16.20 67.96 ± 15.53 59.16 ± 14.38 48.91 ± 13.49 39.68 ± 10.90 48.04 ± 7.10 2.84 ± 2.31 25.17 ± 9.65
MinIP 82.09 ± 15.22 69.87 ± 12.27 60.21 ± 14.97 49.19 ± 16.85 39.91 ± 20.48 47.00 ± 5.79 3.84 ± 3.95 27.32 ± 11.0
SIP 82.09 ± 13.35 66.78 ± 14.42 57.49 ± 13.43 46.87 ± 14.37 38.65 ± 14.06 48.98 ± 4.15 2.94 ± 2.30 25.99 ± 8.68
Dose−acc 72.65 ± 21.56 54.97 ± 20.44 44.05 ± 19.15 37.14 ± 20.41 29.26 ± 22.01 46.07 ± 7.72 2.62 ± 2.22 21.82 ± 8.31
P1 0.004 0.002 0.011 0.017 0.002 0.015 0.016 0.011
P2 0.001 0.001 0.020 0.006 0.001 0.001 0.013 0.003
P3 0.006 0.002 0.020 0.047 0.036 0.041 0.001 0.031
P4 0.001 0.008 0.012 0.036 0.009 0.004 0.002 0.027
P1 –P4 represent the Dose−acc and MIP, AIP, MinIP, and SIP images; values were derived from the Wilcoxon non-parametric test.
Dosimetric Changes in the LAD radiotherapy for left breast cancer increased the probability of
Contrary to the LV, the dose-volume indices of the LAD were ischemic heart disease, pericarditis and valvular disease. Darby
significantly different from those of the Dose−acc in four special et al. (11) showed that in radiotherapy for breast cancer, the
reconstruction images. In the MIP images, the change rates of average cardiac dose was positively correlated with the risk of
V5 , V10 , V20 , V30 , V40 , Dmax , Dmin , and Dmean were 3.6–19.2%, coronary artery disease, and the risk of coronary artery injury
and the smallest change rate was that of Dmax ; in the AIP images, increased by 7.4% with the increase of cardiac dose by 1 Gy.
the change rates of the above indexes were 3.0–28.1%, and the The study of Darby et al. (11) also showed that radiotherapy for
smallest change rate was that of Dmax ; in the MinIP images, the left breast cancer increased the risk of ischemic heart disease,
change rates were 2.0–18.5%, and the smallest change rate was pericarditis, and valvular disease. Therefore, in radiotherapy for
that of Dmax ; in the SIP images, the change rates were 3.4–20.4%, left breast cancer, an accurate assessment of the cardiac dose and
and the smallest change rate was that of Dmax . The details are its substructure is helpful for accurately predicting the occurrence
shown in Table 3. probability of radiation-induced cardiac injury and reduce the
injury by adjusting the radiotherapy plan or clinical intervention.
It is also helpful for improving the quality of life and survival rate
DISCUSSION of patients.
In radiotherapy for breast cancer, especially left breast cancer,
Heart injury is one of the main complications of radiotherapy heartbeat movement is the main cause of an inaccurate dose
for left breast cancer (8, 9). Mcgale et al. (10) showed that assessment of the heart and its substructures (12, 13). A number
Frontiers in Oncology | www.frontiersin.org 4 March 2020 | Volume 10 | Article 433Su et al. Evaluation the Cardiac Dose for BC of scholars have shown that deep inspiratory breath holding of the MIP image differed slightly from that of the Dose−acc , (DIBH) and autonomous breath control (ABC) techniques can reflected mainly in the change rate of V5 , V30 , V40 , and Dmean reduce exposure from breast cancer radiotherapy (14–17). being respiratory movement, cardiac activity is also an important factor 0.05). On MinIP and SIP images, only the change rates of Dmax affecting the accuracy of treatment. The ECG 4D-CT series and Dmean were
Su et al. Evaluation the Cardiac Dose for BC
201809021). Medical record review was performed in accordance QL helped perform the analysis with constructive discussions.
with Institutional Ethics Review Board guidelines. XQ guides the writing of the article.
AUTHOR CONTRIBUTIONS FUNDING
YY contributed to the conception of the study. GG contributed This work was supported by Key Research and Development Plan
significantly to analysis and manuscript preparation. MS of Shandong Province (2018GSF118048) and Key Research and
performed the data analyses and wrote the manuscript. YT and Development Plan of Shandong Province (2018GSF118006).
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